Neonatal androgenic stimulation and adult sexual behavior in male and female golden hamsters.

Neonatally and adult castrated male hamsters as well as neonatally androgenized and nonandrogenized female hamsters were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult animals administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated animals. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens were discussed.     

Evolutionary Neuroandrogenic Theory and Universal Gender Differences in Cognition and Behavior

A theory is proposed that predicts the existence of numerous gender differences in cognition and behavior. The basis for these expectations is the single assumption that females have evolved tendencies to form long term sociosexual alliances with a competent resource provisioner. This assumption is teamed with evidence that males are actually a variant on the female sex with brains masculinized in ways that help them respond to female mating preferences. To orchestrate male responses to female biases in mates, the theory asserts that androgens (male sex hormones) have two main effects on human brain functioning. One is a diminished sensitivity to most environmental stimuli. The other involves shifting cognitive functioning away from the left hemisphere toward a more even and task-specialized hemispheric distribution. Many of the cognitive and behavioral differences between males and females predicted by the theory are described.     

Androgens and aggressive behavior in primates: A review

This review deals with possible central and peripheral effects of androgens upon primate aggressive behavior. One problem that clouds interpretation of experimental work is that measurements of dominance have often been employed, such as competition tests for food and water. Such measures often do not correlate with those obtained by quantifying aggressive interactions. It should be remembered that very few of the 188 primate species have been studied experimentally and that great behavioral and physiological diversity occurs within the order. Therefore, generalizations about the effects of androgens upon aggressive behavior in primates (including man) should be made with caution. Testosterone has an organizing influence upon the foetal brain of rhesus monkeys and may affect the development of neural mechanisms which govern aggression in males. More data are required on primates, however, since rhesus monkeys show some important differences from rodents as regards the effects of androgen upon sexual differentiation of the hypothalamus. In future, marmosets may provide a suitable model for such studies, because there is evidence that sexual differentiation of brain by androgen occurs postnatally in these monkeys. At puberty, male primates show a variety of behavioral changes and, during adulthood, males of seasonally breeding species may be more aggressive during the mating season, when testosterone levels are maximal. This does not indicate a causative relationship between testosterone and aggressive responses, because castration and androgen treatments have little effect upon aggression in prepubertal or adult males of several primate species. Androgens have pronounced effects on sexual responses in adult male monkeys, but their central effects upon aggression are much less important than among rodents. Elec trical stimulation of hypothalamic pathways has been employed to evoke aggressive behavior in marmosets and rhesus monkeys. In the rhesus, preliminary evidence indicates that such pathways show some sensitivity to androgens. In rodents it is known that these areas are richly supplied with monoaminergic neurons, which play an important role in aggressive behavior. There is little evidence on primates, however, and this remains a crucial topic for future research. Peripheral effects of androgens should also be considered. Many prosimians and New World monkeys use scent-marking behaviors and, in males, androgen-dependent chemical cues may be involved in sexual recognition and territorial behavior. This possibility awaits investigation. Finally, plasma testosterone levels may alter as a function of aggression itself; thus levels decrease if male rhesus monkeys are defeated by conspecifics. This might occur because neural events associated with giving (or receiving) aggression also influence pituitary function and hence alter gonadal testosterone secretion. Theoretically, it is possible that such changes in circulating testosterone might affect aggressive behavior via a feedback action on the brain, but the experimental evidence does not support such a view.     

Endocrine Mediators of Masculinization in Female Mammals

ABSTRACT— Most mammal species show traditional patterns of sexual dimorphism (e.g., greater male size and aggression), the proximal mechanism of which involves the male's greater pre- and postnatal exposure to circulating androgens. But in several species, females diverge from the traditional pattern, converging on the male form or even reversing sexual dimorphisms. Such "masculinized" females might show elongation of the clitoris, enhanced body size, and aggressively mediated social dominance over males, and they are interesting case studies for examining the role of androgens in females. This review addresses our understanding of the mediating mechanisms of morphological and behavioral development in both traditional and exceptional mammal species. Although certain lines of evidence implicate testosterone in female masculinization, the role for sex steroids in female development remains unclear. The results call for continued study of both hormonal and nonhormonal mechanisms of sexual differentiation, particularly focused on active processes of feminine development.     

Corpus callosum size is linked to dichotic deafness and hemisphericity, not sex or handedness

Individuals differ in the number of corpus callosum (CC) nerve fibers interconnecting their cerebral hemispheres by about threefold. Early reports suggested that males had smaller CCs than females. This was often interpreted to support the concept that the male brain is more "lateralized" or "specialized," thus accounting for presumed male predominance in mathematics, as well as for aggressive behavior. Ultimately, meta-analyses of these many reports found no significant overall sex differences in inter-cerebral information carrying capacity. Here, using quantitative MRI, we found the midline CC area of 113 subjects was significantly correlated, not with handedness or sex, but with dichotic deafness, and even more so with redefined hemisphericity, the latter accounting for over 19% of CC variability. That is, both dichotic hearing and right brain-oriented individuals of either sex had significantly larger CCs than dichotically deaf or left brain-oriented persons. Thus, current traditions of brain laterality and gender may benefit from revisions that include redefined hemisphericity.     

Smaller splenium in children with nonverbal learning disability compared to controls,high-functioning autism and ADHD

The current study investigated morphological differences in the corpus callosum in children ages 8 to 18 years old with nonverbal learning disability (NLD; n = 19), high-functioning autism (HFA; n = 23), predominantly inattentive ADHD (ADHD:PI; n = 23), and combined type ADHD (ADHD:C; n = 25), as well as those demonstrating typical development (n = 57). Midsagittal area of the corpus callosum and five midsagittal anterior-to-posterior corpus callosum segments were examined using magnetic resonance imaging. Controlling for midsagittal brain area and age, no group differences were found for total corpus callosum area. This finding indicates that higher functioning children on the autistic spectrum do not have smaller corpus callosi as has been found in previous research with heterogeneous samples. Following segmentation of the corpus callosum, the NLD group was observed to have significantly smaller splenia compared to all other groups. Smaller splenia in the NLD group was associated with lower WASI PIQ scores but not WASI VIQ scores. Children with HFA were observed to have larger midbody areas than children with NLD and neurotypically developing children. Children with HFA and NLD demonstrated behavioral symptoms of inattention and hyperactivity similar to the ADHD groups indicating that corpus callosum differences seen in the NLD and HFA groups are not related to these behaviors.     

Sex steroids and human behavior: implications for developmental psychopathology

In a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.     

Sexual cycles in female dogs treated with androgen during development

This experiment was conducted to study hormonal and behavioral cycles in female dogs exposed to androgen during development. The four groups, each consisting of five subjects, were "Normal" females, "Prenatal" females exposed to testosterone propionate (TP) before birth, "Postnatal" females injected with TP for 3 months postpartum, and "Prepost" females exposed to TP in utero and again to testosterone for 4--6 weeks after birth. All Normal females had two estrous cycles during which they showed vaginal bleeding, ovulation, progesterone (P) secretion, sexual receptivity, and were attractive to males. All androgen-treated females showed at least 1 cycle with ovulation and P secretion. Three Postnatal females developed the delayed anovulatory syndrome. Genital bleeding through the vagina (Postnatal group), or through the "penis" (Prenatal and Prepost groups), occurred in 4 Postnatal, 3 Prenatal, and 1 Prepost female. Attractiveness for males was observed in all Prenatal and Postnatal females, but in no Prepost subject. Receptivity was present in four of five Prenatal females but not in any Postnatal or Prepost female. Occurrence of cycles in treated females indicated functional integrity and sensitivity to estrogen in brain mechanisms producing gonadotropin-releasing hormones. Absence of receptivity is referred to diminished responsiveness to ovarian hormones in brain mechanisms mediating receptive behavior. Absence of genital bleeding and lack of attractivity are due to lowered response to estrogen in uterine and vaginal epithelium which results in reduced extravasation of blood, and in failure to secrete the putative "pheromonal" agent normally responsible for attractiveness.     

Hormonal control of sexual attraction in pseudohermaphroditic female dogs

Groups of female dogs exposed to different degrees of androgenic stimulation during development and a control group of ovariectomized females were tested for their attraction to tethered male and female stimulus animals. Attraction to the male was measured before and after administration of estradiol, and attraction to an estrous female was tested before and after administration of testosterone propionate (TP). Time spent visiting the tethered male was approximately equal for all groups prior to hormone treatment, but after receiving estradiol, control females exhibited a pronounced increase in visiting time; the second longest visits were paid by females that had received moderate amounts of androgen before birth; more heavily androgenized females exhibited no increase in attraction to the male despite estradiol injections. Visits to the estrous female before administration of TP were longer for some groups than for others, but there was no relation between the degree of perinatal androgenization and mean visiting time. After injections to TP the most pronounced increase in visiting was shown by females that had received the largest amounts of androgen during development, and the second largest increase occurred in the prenatally androgenized group. Control females showed the smallest increase in visiting time.     

Early experience of sex hormones as a predictor of reading, phonology, and auditory perception

Previous research has indicated possible reciprocal connections between phonology and reading, and also connections between aspects of auditory perception and reading. The present study investigates these associations further by examining the potential influence of prenatal androgens using measures of digit ratio (the ratio of the lengths of the index and ring fingers). Those with low digit ratios (shorter index finger and therefore in the masculine direction) are hypothesised to have experienced greater "masculinisation" in the uterus. ANCOVA analyses using a verbal reasoning task as a covariate showed that only phonology was influenced by digit ratio in the right hand indicating that hypothesised androgen effects were inhibiting phonology; however this effect in the left hand was reduced and instead there was an effect indicating an inhibition of androgens on reading. Furthermore, subjects with low right-hand digit ratios were also impaired compared to those with high right-hand digit ratios in an auditory saltation task. These findings are discussed in terms of the possible effects of androgens on early brain development impairing aspects of the temporal processing of sounds by the left hemisphere, which could also have a secondary influence on developing phonology and literacy skills.     

Endogenous testosterone concentration, mental rotation, and size of the corpus callosum in a sample of young Hungarian women

In the present study brain laterality, hemispheric communication, and mental rotation performance were examined. A sample of 33 women were tested for a possible linear relationship of testosterone level and mental rotation with structural background of the brain. Subjects with a smaller splenial area of corpus callosum tended to have lower levels of testosterone (r =.37, p<.05). However, there were no significant differences in mean scores of mental rotation of object and hand between groups with high and low levels of testosterone. There was a significant difference in relative size of the 6th area (slice) of the corpus callosum between groups with good and poor scores on mental rotation of an object and also in relative size of the 4th and 5th slices of the corpus callosum between groups on mental rotation of the hand. The good and poor scorers' show different relations with the measures of the corpus. The mental rotation of hand was associated with the parietal areas of the corpus callosum, while the mental rotation of object was associated only with the occipital area. These observations suggest that higher testosterone levels may be associated with a larger splenial area, which represents an important connection between the parieto-occipitocortical areas involved in activation of mental images. Further srudy is encouraged.     

Sex differences in the effects of gonadectomy on amphetamine-induced rotational behavior in rats

The effects of gonadectomy on amphetamine-induced rotational behavior were studied in male and female rats. Different systemic doses were used to produce equivalent brain concentrations of the drug in each group, thereby controlling for sex differences in the metabolism of amphetamine. Ovariectomy of female rats significantly attenuated amphetamine-induced rotation, whereas castration of males was without effect. The results support the idea that in females, the endogenous gonadal hormones facilitate functional activity in the mesostriatal dopamine system.     

Baby babbling at five months linked to sex hormone levels in early infancy

Gender-dependent differentiation of the brain at morphological, neurochemical and functional levels of organization have been shown to be primarily controlled by sex differences in gonadal hormone concentrations during pre- and early postnatal development. Indeed, previous studies have reported that pre- and perinatal hormonal environments influence brain development and, consequently, affect sex specific long-term language outcomes.Herein, we investigated whether postnatal surges of estrogen (estradiol) and androgen (testosterone) may predict properties of pre-speech babbling at five months. This study is the first attempt to investigate a possible correlation between sex hormones and infants’ articulatory skills during the typical postnatal period of extended hormonal activity known as ‘mini-puberty.’ A hierarchical, multiple regression approach revealed a significant, robust positive relationship between 4-week concentrations of estradiol and individual articulatory skills. In contrast, testosterone concentrations at five months negatively correlated with articulatory skills at the same age in both boys and girls. Our findings reinforce the assumption of the importance of sex hormones for auditory–vocal development towards language in human infants.     

Sex differences in the adolescent brain

Adolescence is a time of increased divergence between males and females in physical characteristics, behavior, and risk for psychopathology. Here we will review data regarding sex differences in brain structure and function during this period of the lifespan. The most consistent sex difference in brain morphometry is the 9–12% larger brain size that has been reported in males. Individual brain regions that have most consistently been reported as different in males and females include the basal ganglia, hippocampus, and amygdala. Diffusion tensor imaging and magnetization transfer imaging studies have also shown sex differences in white matter development during adolescence. Functional imaging studies have shown different patterns of activation without differences in performance, suggesting male and female brains may use slightly different strategies for achieving similar cognitive abilities. Longitudinal studies have shown sex differences in the trajectory of brain development, with females reaching peak values of brain volumes earlier than males. Although compelling, these sex differences are present as group averages and should not be taken as indicative of relative capacities of males or females.     

Genotype modulates prenatal stress effects on aggression in male and female mice

Prenatal stress (heat and restraint) significantly increased postpartum aggression (proportion of animals fighting and/or the intensity of the behavior) in C57BL/6J female mice and reduced the behavior in DBA/2J females. For intermale aggression, prenatal stress increased the behavior (intensity of aggression) in C57BL/6J males but did not affect aggressive behavior in DBA/2J animals. Infanticidal behavior (the killing of young) exhibited by male mice was not influenced by prenatal stress in either strain. Relative anogenital distance measurements in neonates at birth did not serve as a reliable predictor of strain variation in prenatal stress effects. Prenatal stress did not influence this measure of prenatal androgen exposure in DBA/2J or C57BL/6J females. For males, prenatal stress elevated relative anogenital distance in C57BL/6J mice and decreased this measure in DBA/2J animals. Prenatal stress effects on aggressive behavior in male and female mice therefore depend upon genotype. Strain-dependent differences may be modulated by differences in endocrine reactivity to prenatal stress/and or differential central neural tissue sensitivity to hormones.     

Bilingual corpus callosum variability

Magnetic resonance imaging was used to produce midsagittal images of the corpus callosum of 19 right-handed adult male and female subjects. The preliminary findings of this study indicate that significant adaptation in the anterior midbody of the corpus callosum has occurred to accommodate multiple language capacity in bilingual individuals compared to monolingual individuals. The main interpretation of this finding is that the precentral gyrus is involved in bilingual faculty adaptation assuming a role consistent with the somatotopical input to areas dedicated to the mouth, and input to association tracts connecting the premotor and supplementary motor cortices. This paper discusses possible implications to neuroscientists, second language educators, and their students.     

Fetal alcohol syndrome and the developing socio-emotional brain

Fetal alcohol syndrome (FAS) is currently recognized as the most common known cause of mental retardation, affecting from 1 to 7 per 1000 live-born infants. Individuals with FAS suffer from changes in brain structure, cognitive impairments, and behavior problems. Researchers investigating neuropsychological functioning have identified deficits in learning, memory, executive functioning, hyperactivity, impulsivity, and poor communication and social skills in individuals with FAS and fetal alcohol effects (FAE). Investigators using autopsy and brain imaging methods have identified microcephaly and structural abnormalities in various regions of the brain (including the basal ganglia, corpus callosum, cerebellum, and hippocampus) that may account for the neuropsychological deficits. Results of studies using newer brain imaging and analytic techniques have indicated specific alterations (i.e., displacements in the corpus callosum, increased gray matter density in the perisylvian regions, altered gray matter asymmetry, and disproportionate reductions in the frontal lobes) in the brains of individuals prenatally exposed to alcohol, and their relations with brain function. Future research, including using animal models, could help inform our knowledge of brain-behavior relations in the context of prenatal alcohol exposure, and assist with early identification and intervention.     

Perinatal exposure to diethylstilbestrol improves olfactory discrimination learning in male and female Swiss-Webster mice

During late prenatal and early postnatal brain development, estrogen induces structural sex differences that correspond to behavioral differences in certain domains such as learning and memory. The typically superior performance of males is attributed to the action of elevated concentrations of estrogen, derived inside neurons from the aromatization of testosterone. In contrast, female performance appears dependent on minimal estrogenic activity. Rat models of the relationship between hormones and cognitive behavior predominate the field, but the advent of genetically modified mice as research tools necessitates development of analogous mouse models. This study examined how early postnatal exposure to the synthetic estrogen diethylstilbestrol (DES) affected the ability of male and female Swiss-Webster mice to learn a two-choice olfactory discrimination and three repeated reversals. Mice treated with subcutaneous injections of DES from postnatal days 1-10 learned reversals more readily than oil-treated controls, a difference that became evident after repeated testing. DES-exposed males and females learned reversals at a comparable rate, suggesting that early postnatal estrogen exposure does not influence this mode of learning through a sexually differentiated mechanism in mice. An analysis of response patterns during qualitatively different phases of reversal learning revealed that DES-induced improvements probably were not due to greater inhibitory control. Instead, DES appeared to enhance associative ability. Early postnatal estrogen exposure may have the potential to preserve certain cognitive skills in adulthood.     

Another psychobiological view of sexual differentiation

The major psychobiological theory of sex differences is based on the hypothesis that hormones induce sex differences in neural organization. Hormonally masculinized or feminized brains are thought to underlie subsequent behavioral sex differences. This theory and the constructs, arguments, and evidence used in its support are closely examined. Some conceptual problems with widely used arguments are identified and discussed. Behavioral, physiological, and anatomical evidence from studies of animal sexual behavior is reviewed. It is concluded that the evidence fails to support generally accepted views that early hormones affect behavior through direct effects on brain differentiation and that behavioral differences must be located in the brain. It is argued instead that hormones coact and interact with other factors throughout development, that brain differences may result from as well as cause functional differences, and that hormone-based sources of sex differences may be located throughout the body and in the social surround. Directions for new research are suggested and implications for interpretation of human sex differences are discussed.     

Age-related differences in interhemispheric visuomotor integration measured by the redundant target effect

Presentation of bilateral redundant visual stimuli produces faster reaction times (RT) than presentation of a single unilateral stimulus; an effect known as the redundant target effect (RTE; Miller, 1982), and is a means of testing interhemispheric visuomotor integration (Ouimet, 2009). RTEs that exceed expectations, based on Miller's race model of inequality (RMI), are referred to as "enhanced RTEs" and imply neural coactivation. Paradoxically, enhanced RTEs are observed in cases of corpus callosum disruption. The Hemispheric Coactivation Hypothesis accounts for this paradox by positing that bihemispheric processing occurs to both unilateral and bilateral stimuli in the normal brain, but occurs only with bilateral stimuli in the disconnected brain. Neuroimaging has revealed decreases in the microstructural integrity of the corpus callosum with age (Ota et al., 2006), but research investigating the bilateral RTE in healthy older individuals is lacking. The present study investigated the bilateral RTE in healthy younger and healthy older adults using simple RT and choice RT tasks. Our prediction that older individuals would show significantly larger RTEs than younger individuals was found to be true for both tasks. Tests of the RMI produced little evidence for coactivation. The crossed-uncrossed difference, generally used as a means of testing visuomotor interhemispheric transfer, was also investigated, but no age effects were found. The observation of greater RTE in age is congruent with the Hemispheric Coactivation hypothesis (Miller, 2004) in which callosal disconnection is associated with increased RTE.